1. Field of the Invention
This invention relates generally to compounds which are effective as catalysts for dismutation of superoxide.
2. Description of Related Art
Superoxide dismutase is an enzyme that catalyzes the conversion of superoxide into molecular oxygen and hydrogen peroxide to provide a first line of defense against superoxide and reactive oxygen metabolites derived from superoxide. Such reactive oxygen metabolites are known to contribute to the numerous tissue pathologies including those involved in inflammatory diseases and disorders. Recently, the nonpeptidyl mimetics of superoxide dismutase have been identified (see for example, U.S. Pat. No. 6,214,817 to Riley et al.). These superoxide dismutase mimetics have been shown to be effective in various diseases including inflammation (Salvemini et al., Science 286:304-306, 1999; Salvemini et al., Arthritis & Rheumatism 44:2909-2921, 2001).
The natural occurring superoxide dismutase protein has been conjugated to various substances and, in particular, to polyethylene glycol (for review see Veronese et al., Adv. Drug Deliv. Rev. 54:587-606, 2002). Nevertheless, conjugation of superoxide dismutase mimetics with polymeric substances having molecular weights lower than those in the million Da range have not been heretofore disclosed.